I-cell disease or mucolipidosis II is a childhood disorder that is believed to be transferred in an autosomal recessive manner. The disease is characterized by severe psychomotor retardation, early cessation of growth in stature, minimal skeletal deformities, mild or no hepatic enlargement, absence of excessive excretion of mucopolysaccharides and the presence of numerous cytoplasmic inclusion bodies. Since the molecular basis is not known for I-cell disease, our research efforts involve several different approaches aimed at elucidating information concerning the nature of the defect at the protein level. Studies are in progress to characterize the Beta-D-galactosidase activity in I-cell tissue, urine and cultured fibroblasts with respect to its electrophoretic (starch gel and isoelectric focusing) and kinetic properties. Similar experiments are being carried out with alpha-L-fucosidase. In addition, affinity column procedures developed in our laboratory will be used to isolate and characterize (physical and chemical) both the normal and I-cell beta-D-galactosidase and alpha-L-fucosidase proteins.